Although stem cells hold considerable promise for the treatment of a number of devastating diseases via cell replacement therapy, such as cardiovascular diseases, neurodegenerative diseases, diabetes and cancers, obstacles such as control of stem cell fate, immuno-rejection, and limited cell sources must be overcome before their therapeutic potentials can be realized. This requires a better understanding of the signaling pathways that control stem cell fate and an improved ability to manipulate stem cell proliferation and differentiation. The ability to dedifferentiate or reverse lineage-committed cells to multipotent progenitor cells might overcome many of the obstacles associated with using embryonic stem cells and adult stem cells. The purpose of this proposal is to develop and carry out high throughput cellular phenotypic screens of combinatorial chemical library and arrayed siRNA library to identify small molecules and genes, which can dedifferentiate unipotent myoblasts to become multipotent mesenchymal progenitor cells. These studies should enhance our understanding of the underlying molecular mechanisms of these processes, and may ultimately facilitate the therapeutic application of stem cells as well as development of small molecule therapeutics to stimulate tissue regeneration in vivo. [unreadable] [unreadable] [unreadable]